Fragão-Marques Mariana, Vitorino Rui, Barroso Isaac, Falcão-Pires Inês, Leite-Moreira Adelino, Trindade Fábio
UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal.
Department of Clinical of Clinical Pathology, São João University Hospital Centre, 4200-319 Porto, Portugal.
J Pers Med. 2022 Feb 11;12(2):264. doi: 10.3390/jpm12020264.
Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC-MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated ≥2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein-protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis.
心房颤动(AF)是最常见的具有不良临床结局的心律失常。心包积液(PF)因其与心脏的接近性而反映心脏的病理生理状态。本研究旨在对PF蛋白质组进行表征以鉴定新的疾病生物标志物。选取了83例因严重主动脉瓣狭窄接受主动脉瓣置换手术的患者,并记录了他们的基线超声心动图和临床变量。采用鸟枪法(GeLC-MS/MS)和无标记定量方法(LFQ),盲目选择13个样本进行蛋白质组表征。根据既往房颤病史,进行偏最小二乘判别分析(PLS-DA),并确定投影中最重要的前15个变量。为探究潜在生物标志物,利用LFQ数据设计ROC曲线。通过ELISA在心包积液和血清中对目标蛋白进行进一步验证。蛋白质组分析发现9种蛋白质上调和下调≥2倍。膜联蛋白A1、膜联蛋白A2和波形蛋白是PLS-DA中用于组间区分的前15个最重要变量之一。蛋白质-蛋白质相互作用和基因本体富集分析显示了已鉴定蛋白质之间的功能相互作用,这些蛋白质均为粘着斑位点的一部分。通过ELISA定量时,膜联蛋白A1在房颤患者的心包积液中升高,但在血清中未升高。膜联蛋白A1是严重主动脉瓣狭窄患者房颤的一种新型心包积液生物标志物。